Modelo de sección eficaz para la ruptura de ADN bajo la acción simultánea de hipertermia y radiación ionizante

Abstract

Cancer is a major public health problem, despite the increase in the average survival of patients diagnosed early. It is of course necessary to combine efforts and resources in its prevention, treatment or cure, thus alleviating the difficult situation that around 20 million people in the world are going through, in 2020 alone, of which a little more survive. of half [1]. Since the 1980s it has been shown that localized hyperthermia (HT) between 40° - 42.5°C on affected tissue increases the therapeutic efficiency of radiotherapy (RT) and more recent studies show that it has the potential to improve the life expectancy of patients. cancer patients, especially when RT and HT are applied simultaneously [2]. In this sense, HT has proven to be one of the most powerful radio-sensitizers known to date [3], achieving a significant decrease in the dose of ionizing radiation required on tumor tissue to achieve its control. As a consequence, better therapeutic results can be obtained with fewer side effects in the long and medium term. However, the simultaneous application of HT and RT is not an easy task in clinical routines due to the lack of precision technologies that allow both forms of energy to be deposited synchronously [11]. For this reason, combination therapy is often given sequentially, at the expense of significant reductions in the sensitizing power of HT over RT [2]. In this direction, the inoculation of the tumor with gold nanoparticles constitutes an interesting alternative with the potential to make the simultaneous deposition of both forms of energy feasible. This therapy consists of introducing nanoparticles into the tissue to be treated, and then subjecting it to infrared radiation and/or ionizing radiation [4]. Since radiation decay times are longer than cooling times, this work hypothesizes that the RT->HT sequence could preserve the synergy of simultaneous treatment under certain conditions. From a mechanistic point of view, The most accepted hypothesis to explain the synergy between both therapies is based on the thermal denaturation of the repair proteins of DNA damage induced by ionizing radiation [5,6]. However, this explanation fundamentally rules out the possibility that the two forms of energy may physically interact and that this interaction may be responsible for at least part of the additional synergistic effect that is obtained when the therapies are administered at the same time. We propose that this additional interaction exists during the simultaneous application of the two treatments, and that the effect may be due to the change in the cross section of collision between the particles of the ionizing radiation field (or the ions produced by it) [7] and DNA molecules, when the DNA oscillates due to the increase in temperature. This degree work aims to formulate a mathematical model that constitutes a plausible explanation for the pronounced synergy factor between therapies administered synchronously.